A W/O cream base which comprises an oily external phase and thus exerts an effect of protecting the skin is superior to an O/W one as a base for a remedy for skin diseases. However, O/W cream base preparations containing remedies for skin diseases have been often used hitherto, while W/O cream preparations have been scarcely employed. This is because the conventional W/O cream bases contain a large amount of oily phase, components and thus are inferior to the O/W cream bases in the comfort in the use and the stability of preparation. When an active ingredient is blended with a W/O cream base of a high moisture content, in particular, the comfort in the use is improved but the heat stability of the preparation is deteriorated. Thus no satisfactory cream preparation has been obtained so far.
Examples of the prior art cream preparations containing ketotifen or its fumarate include Japanese Patent Application Laid-Open Gazette Nos. Sho. 51-32724, Sho. 51-142543, Sho. 62-164624, Hei. 1-102024 and Hei. 1-121218. However none of these cream preparations containing ketotifen or its fumarate disclosed in the above references is satisfactory from the viewpoints of the stability of the preparations and drug and the percutaneous absorption of the drug.
The conventional W/O cream base contains a very large amount of an oily phase, i.e., the external phase. When applied to the skin, therefore, it poorly dries and has a persistent stickiness, thus being uncomfortable. Furthermore, it is apt to cause liquid separation due to the high content of the oily phase, which means that it has a poor stability. In addition, it shows only a poor release of the active ingredient from the preparation. Therefore, it has been urgently required to develop a W/O cream preparation capable of effectively releasing a drug from the viewpoint of pharmacological effects too. Accordingly, it is an object of the present invention to provide a W/O cream preparation which is comfortable in the use, has a high stability and effectively releases the drug.
For instance, when ketotifen having a high chemical activity is added to the conventional cream base, the active ingredient, i.e., ketotifen or its fumarate, reacts with the components of the cream base or impurities contained therein and thus causes a decrease in the content of the active ingredient or a color change with the lapse of time. Furthermore, it is sometimes observed that the cream is degraded into an emulsion or causes liquid separation. In the case of a W/O cream preparation which is inherently inferior to an O/W one in stability, in particular, it is highly difficult to maintain a preparation containing ketotifen or its fumarate in a stable state.
Accordingly, it is another object of the present invention to provide: (1) a stable W/O cream preparation containing ketotifen or its fumarate; and (2) a cream preparation excellent in the percutaneous absorption of ketotifen or its fumarate.